Post-Graduate Program in Morphological Sciences, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil; National Institutes of Health, USA; University of Pittsburgh, USA.
National Institutes of Health, USA; University of Pittsburgh, USA.
Neuroimage. 2020 Aug 15;217:116875. doi: 10.1016/j.neuroimage.2020.116875. Epub 2020 Apr 23.
Corpus callosum dysgenesis (CCD) is a developmental brain condition in which some white matter fibers fail to find their natural course across the midplane, reorganizing instead to form new aberrant pathways. This type of white matter reorganization is known as long-distance plasticity (LDP). The present work aimed to characterize the Balb/c mouse strain as a model of CCD. We employed high-resolution anatomical MRI in 81 Balb/c and 27 C57bl6 mice to show that the Balb/c mouse strain presents a variance in the size of the CC that is 3.9 times higher than the variance of normotypical C57bl6. We also performed high-resolution diffusion-weighted imaging (DWI) in 8 Balb/c and found that the Balb/c strain shows aberrant white matter bundles, such as the Probst (5/8 animals) and the Sigmoid bundles (7/8 animals), which are similar to those found in humans with CCD. Using a histological tracer technique, we confirmed the existence of these aberrant bundles in the Balb/c strain. Interestingly, we also identified sigmoid-like fibers in the C57bl6 strain, thought to a lesser degree. Next, we used a connectome approach and found widespread brain connectivity differences between Balb/c and C57bl6 strains. The Balb/c strain also exhibited increased variability of global connectivity. These findings suggest that the Balb/c strain presents local and global changes in brain structural connectivity. This strain often presents with callosal abnormalities, along with the Probst and the Sigmoid bundles, making it is an attractive animal model for CCD and LDP in general. Our results also show that even the C57bl6 strain, which typically serves as a normotypical control animal in a myriad of studies, presents sigmoid-fashion pattern fibers laid out in the brain. These results suggest that these aberrant fiber pathways may not necessarily be a pathological hallmark, but instead an alternative roadmap for misguided axons. Such findings offer new insights for interpreting the significance of CCD-associated LDP in humans.
胼胝体发育不良（CCD）是一种发育性脑疾病，其中一些白质纤维未能在中线上找到其自然通路，而是重新组织形成新的异常通路。这种白质重组织形式被称为长程可塑性（LDP）。本研究旨在将 Balb/c 小鼠品系鉴定为 CCD 模型。我们使用高分辨率解剖学 MRI 对 81 只 Balb/c 和 27 只 C57bl6 小鼠进行了研究，结果表明 Balb/c 小鼠品系的 CC 大小差异是 C57bl6 正常小鼠的 3.9 倍。我们还对 8 只 Balb/c 小鼠进行了高分辨率弥散加权成像（DWI）研究，发现 Balb/c 品系存在异常的白质束，如 Probst（5/8 只动物）和 Sigmoid 束（7/8 只动物），类似于人类 CCD 患者。通过组织学示踪技术，我们在 Balb/c 品系中证实了这些异常束的存在。有趣的是，我们还在 C57bl6 品系中发现了类似的 Sigmoid 样纤维，但其程度较轻。随后，我们使用连接组学方法发现 Balb/c 和 C57bl6 品系之间存在广泛的脑连接差异。Balb/c 品系还表现出全局连接变异性增加。这些发现表明 Balb/c 品系的脑结构连接存在局部和全局变化。该品系经常出现胼胝体异常，以及 Probst 和 Sigmoid 束，使其成为 CCD 和 LDP 的理想动物模型。我们的研究结果还表明，即使是 C57bl6 品系，通常作为众多研究中的典型对照动物，其大脑中也存在 Sigmoid 样纤维排列。这些结果表明，这些异常纤维通路可能不一定是病理性特征，而是误导轴突的另一种替代路径。这些发现为解释人类 CCD 相关 LDP 的意义提供了新的视角。
